We propose to study the effect of local ocular factors on the pathogenesis and control of herpes simplex virus (HSV) infections of the eye. In the experiments proposed here we will: (1) Test corneal specimens from patients with herpetic eye disease and from control cases to reveal latent virus infection of the cornea; (2) develop animal models of corneal latency; (3) examine the effect of topical (local) mediators, particularly adrenergic drugs, on recurrent viral shedding from the eye in experimental animal models; (4) evaluate the effect of these same mediators on HSV replication in corneal organ culture and cell culture systems. To prevalence and pathogenesis of latent HSV in cornea will be determined by co-cultivation and immunochemical staining of corneas removed from patients with herpetic eye disease at keratoplasty. We will also develop an in vitro model of HSV latency in animal corneas and compare reactivation in infected corneas and ganglia. We will also study the ocular shedding of virus in latently infected animals following locally applied adrenergic drugs and other mediators (e.g. prostaglandins, interferons) to test the hypothesis that local factors specifically affect the ability of the ocular tissues to support HSV replication. These compounds will be tested in latently infected animals, corneal organ cultures and cell culture systems. The goal of this research is to examine local treatment with specific mediators for their potential to prevent or enhance recurrent herpetic eye disease in humans.